Avsar Rusen, Gurer Turkan, Aytekin Alper
Department of Biology, Faculty of Art and Science, Gaziantep University, 27310, Gaziantep, Turkey.
Department of General Surgery, Faculty of Medicine, Gaziantep University, 27310, Gaziantep, Turkey.
J Cancer. 2023 Jul 31;14(13):2399-2409. doi: 10.7150/jca.86974. eCollection 2023.
MicroRNAs (miRNAs) have important function in cancer development and progression. This study aims to determine the expression levels of miR-639, miR-641, miR-1915-3p, and miR-3613-3p in tissues of colorectal cancer (CRC) patients and the role of these miRNAs in the CRC pathogenesis. Tumor and non-tumor tissues were collected from a total of 59 CRC patients. qRT-PCR was used to identify the expressions of miR-639, miR-641, miR-1915-3p and miR-3613-3p. Through bioinformatics analysis, the target genes of miRNAs were identified by using DIANA mirPath v.3. Signaling pathways were generated using KEGG pathway database. Biological pathway, cellular component analysis, and analysis of Protein-Protein Interactions (PPI) Networks were performed using FunRich and STRING database. Our findings revealed that miR-639, miR-641 and miR-3613-3p were significantly downregulated, and miR-1915-3p was significantly upregulated in tumor tissues compared to non-tumor tissues (˂0.05). Furthermore, MAPK signaling pathway was the most enriched KEGG pathway regulated by miR-639, miR-641, miR-1915-3p and miR-3613-p. According to the FunRich, it was demonstrated that the targeted genes by miRNAs related to the cellular component and biological pathways such as beta-catenin-TCF7L2, axin-APC-beta-catenin-GSK3B complexes, Arf6 signaling, Class I PI3K signaling, etc. And, by the PPI analysis, it was established that the target genes were clustered on and . These outcomes imply that miR-639, miR-641 and miR-3613-3p have tumor suppressor roles, while miR-1915-3p has an oncogenic role in the pathogenesis of CRC. According to the results of the current study, dysregulated miR-639, miR-641, miR-1915-3p, and miR-3613-3p might contribute to the development of CRC.
微小RNA（miRNA）在癌症发生和发展过程中发挥着重要作用。本研究旨在测定结直肠癌（CRC）患者组织中miR-639、miR-641、miR-1915-3p和miR-3613-3p的表达水平，以及这些miRNA在CRC发病机制中的作用。共收集了59例CRC患者的肿瘤组织和非肿瘤组织。采用qRT-PCR法检测miR-639、miR-641、miR-1915-3p和miR-3613-3p的表达。通过生物信息学分析，利用DIANA mirPath v.3软件鉴定miRNA的靶基因。使用KEGG通路数据库生成信号通路。利用FunRich软件和STRING数据库进行生物通路、细胞成分分析以及蛋白质-蛋白质相互作用（PPI）网络分析。我们的研究结果显示，与非肿瘤组织相比，miR-639、miR-641和miR-3613-3p在肿瘤组织中显著下调，而miR-1915-3p显著上调（P<0.05）。此外，MAPK信号通路是受miR-639、miR-641、miR-1915-3p和miR-3613-p调控的最丰富的KEGG通路。根据FunRich软件分析结果表明，miRNA的靶基因与细胞成分和生物通路相关，如β-连环蛋白-TCF7L2、轴蛋白-APC-β-连环蛋白-GSK3B复合物、Arf6信号通路、I类PI3K信号通路等。并且，通过PPI分析确定靶基因聚集在……和……上。这些结果表明，miR-639、miR-641和miR-3613-3p在CRC发病机制中具有肿瘤抑制作用，而miR-1915-3p具有致癌作用。根据本研究结果表明，miR-639、miR-641、miR-1915-3p和miR-3613-3p表达失调可能促进CRC的发生发展。
